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SUMMARY:To Clinical Evaluation of MTBVAC: A New Attenuated Tuberculosis Va
 ccine Based on phoP Inactivation 
DTSTART:20120206T130000
DTSTAMP:20260916T045125Z
UID:67000ae7159f4139bfb46f3451ba14a5fcb550bef8b3ede9b18b2138
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof Carlos Martin\nPhoP is essential for intricate virulence 
 networks in M. tuberculosis. The inactivation of phoP gene in M. tuberculo
 sis leads to high attenuation in cellular and animal models. The M. tuberc
 ulosis phoP mutant\, SO2\, is more attenuated than M. bovis BCG Pasteur in
  immunocompromised SCID mice by aerosol and intravenous routes and protect
 ed guinea pigs and non-human primates against tuberculosis infection. A ke
 y aspect of the variable efficacy conferred by BCG may be insufficient ind
 uction of long-lived memory T-cell responses. When compared to M. tubercul
 osis\, M. bovis has deleted many regions of its genome. In addition\, duri
 ng the attenuation process of BCG\, additional genes were lost\, leading t
 o loss of either virulence factors or additional immunodominant antigens. 
 Recent work published by J. Triccas provides data on the mechanism for the
  increased protection afforded by M. tuberculosis phoP-based vaccines. SO2
  Vaccination results in higher expansion and differentiation of antigen-sp
 ecific CD4+ T cells into effector and memory T cells compared to BCG in va
 ccinated mice. Memory T cells were more capable of differentiation into fu
 nctional effector cells upon challenge with M. tuberculosis. In order to d
 evelop a safe and more effective vaccine that could replace BCG\, we have 
 constructed a new live vaccine\, designated MTBVAC\, through the rational 
 attenuation of a M. tuberculosis clinical isolate. MTBVAC is based on two 
 stable independent deletions of two virulence genes\, phoP and fadD26\; de
 letion of fadD26 eliminates DIM synthesis\, a family of lipids linked with
  M. tuberculosis virulence. MTBVAC is the first live attenuated candidate 
 vaccine fulfilling the Geneva consensus requirements for live mycobacteria
 l vaccines. Manufacturer and industrial partner BIOFABRI has finalised a G
 ood Manufacturing Practices grade production process for freeze dried MTBV
 AC live vaccine\, and is ready for clinical trials. Final product MTBVAC h
 as demonstrated attenuation\, safety and protective efficacy in rigorous n
 on-clinical studies\, in agreement with regulatory requirements. Our plan 
 is to progress the live attenuated MTBVAC vaccine candidate to first-in-hu
 man clinical evaluation as part of the of TuBerculosis Vaccine Initiative 
 (TBVI).
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CONFIRMED
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